Bryan A. Cotton

The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies

ABSTRACT Increasing evidence has demonstrated that aggressive crystalloid-based resuscitation strategies are associated with cardiac and pulmonary complications, gastrointestinal dysmotility, coagulation disturbances, and immunological and inflammatory mediator dysfunction. As large volumes of fluids are administered, imbalances in intracellular and extracellular osmolarity occur. Disturbances in cell volume disrupt numerous regulatory mechanisms responsible for keeping the inflammatory cascade under control. Several authors have demonstrated the detrimental effects of large, crystalloid-based resuscitation strategies on pulmonary complications in specific surgical populations. Additionally, fluid-restrictive strategies have been associated with a decreased frequency of and shorter time to recovery from acute respiratory distress syndrome and trends toward shorter lengths of stay and lower mortality. Early resuscitation of hemorrhagic shock with predominately saline-based regimens has been associated with cardiac dysfunction and lower cardiac output, as well as higher mortality. Numerous investigators have evaluated potential risk factors for developing abdominal compartment syndrome and have universally noted the excessive use of crystalloids as the primary determinant. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation. Future resuscitation research is likely to focus on improvements in fluid composition and adjuncts to administration of large volume of fluid.

Damage control hematology: The impact of a trauma exsanguination protocol on survival and blood product utilization

BACKGROUNDnThe importance of early and aggressive management of trauma- related coagulopathy remains poorly understood. We hypothesized that a trauma exsanguination protocol (TEP) that systematically provides specified numbers and types of blood components immediately upon initiation of resuscitation would improve survival and reduce overall blood product consumption among the most severely injured patients.nnnMETHODSnWe recently implemented a TEP, which involves the immediate and continued release of blood products from the blood bank in a predefined ratio of 10 units of packed red blood cells (PRBC) to 4 units of fresh frozen plasma to 2 units of platelets. All TEP activations from February 1, 2006 to July 31, 2007 were retrospectively evaluated. A comparison cohort (pre-TEP) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. Multivariable analysis was performed to compare mortality and overall blood product consumption between the two groups.nnnRESULTSnTwo hundred eleven patients met inclusion criteria (117 pre-TEP, 94 TEP). Age, sex, and Injury Severity Score were similar between the groups, whereas physiologic severity (by weighted Revised Trauma Score) and predicted survival (by trauma-related Injury Severity Score, TRISS) were worse in the TEP group (p values of 0.037 and 0.028, respectively). After controlling for age, sex, mechanism of injury, TRISS and 24-hour blood product usage, there was a 74% reduction in the odds of mortality among patients in the TEP group (p = 0.001). Overall blood product consumption adjusted for age, sex, mechanism of injury, and TRISS was also significantly reduced in the TEP group (p = 0.015).nnnCONCLUSIONSnWe have demonstrated that an exsanguination protocol, delivered in an aggressive and predefined manner, significantly reduces the odds of mortality as well as overall blood product consumption.

Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients.

BACKGROUNDnAlthough known to be an independent predictor of poor outcomes in medical intensive care unit (ICU) patients, limited data exist regarding the prevalence of and risk factors for delirium among surgical (SICU) and trauma ICU (TICU) patients. The purpose of this study was to analyze the prevalence of and risk factors for delirium in surgical and trauma ICU patients.nnnMETHODSnSICU and TICU patients requiring mechanical ventilation (MV) >24 hours were prospectively evaluated for delirium using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). Those with baseline dementia, intracranial injury, or ischemic/hemorrhagic strokes that would confound the evaluation of delirium were excluded. Markov models were used to analyze predictors for daily transition to delirium.nnnRESULTSnOne hundred patients (46 SICU and 54 TICU) were enrolled. Prevalence of delirium was 73% in the SICU and 67% in the TICU. Multivariable analyses identified midazolam [OR 2.75 (CI 1.43-5.26, p = 0.002)] exposure as the strongest independent risk factor for transitioning to delirium. Opiate exposure showed an inconsistent message such that fentanyl was a risk factor for delirium in the SICU (p = 0.007) but not in the TICU (p = 0.936), whereas morphine exposure was associated with a lower risk of delirium (SICU, p = 0.069; TICU p = 0.024).nnnCONCLUSIONnApproximately 7 of 10 SICU and TICU patients experience delirium. In keeping with other recent data on benzodiazepines, exposure to midazolam is an independent and potentially modifiable risk factor for the transitioning to delirium.

Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival.

BACKGROUNDnDespite recent attention and impressive results with damage control resuscitation, the appropriate ratio of blood products to be transfused has yet to be defined. The purpose of this study was to evaluate whether suggested blood product ratios yield superior survival rates.nnnMATERIALSnAfter IRB approval, a retrospective evaluation was performed on all trauma exsanguination protocol (TEP, n = 118) activations from February 1, 2006 to July 31, 2007. A comparison cohort (pre-TEP, n = 140) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. We then compared those who received FFP:RBC (2:3) and platelet:RBC (1:5) ratios with those who did not reach these ratios. Multivariate analysis was performed for independent predictors of mortality.nnnRESULTSnA total of 259 patients were available for study. Patients receiving FFP:RBC at a ratio of 2:3 or greater (n = 64) had a significant reduction in 30-day mortality compared with those who received less than a 2:3 ratio (n = 195); 41% versus 62%, p = 0.008. Patients receiving platelets:RBC at a ratio of 1:5 or greater (n = 63) had a lower 30-day mortality when compared with those with who received less than this ratio (n = 196); (38% vs. 61%, p = 0.001). Regression model demonstrated that a ratio of FFP to PRBC is an independent predictor of 30-day mortality, controlling for age and TRISS (OR 1.78, 95% CI 1.01-3.14).nnnCONCLUSIONSnIncreased FFP:PRBC and PLT:PRBC ratios during a period of massive transfusion improved survival after major trauma. Massive transfusion protocols should be designed to achieve these ratios to provide maximal benefit.

Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications.

INTRODUCTIONnMassive transfusion (MT) protocols have been shown to improve survival in severely injured patients. However, others have noted that these higher fresh frozen plasma (FFP):red blood cell (RBC) ratios are associated with increased risk of organ failure. The purpose of this study was to determine whether MT protocols are associated with increased organ failure and complications.nnnMETHODSnOur institutions exsanguination protocol (TEP) involves the immediate delivery of products in a 3:2 ratio of RBC:FFP and 5:1 for RBC:platelets. All patients receiving TEP between February 2006 and January 2008 were compared with a cohort (pre-TEP) of all patients from February 2004 to January 2006 that (1) went immediately to the operating room and (2) received MT (>or=10 units of RBC in first 24 hours).nnnRESULTSnTwo hundred sixty-four patients met inclusion (125 in the TEP group, 141 in the pre-TEP). Demographics and Injury Severity Score were similar. TEP received more intraoperative FFP and platelets but less in first 24 hours (p < 0.01). There was no difference in renal failure or systemic inflammatory response syndrome, but pneumonia, pulmonary failure, open abdomens, and abdominal compartment syndrome were lower in TEP. In addition, severe sepsis or septic shock and multiorgan failure were both lower in the TEP patients (9% vs. 20%, p = 0.011 and 16% vs. 37%, p < 0.001, respectively).nnnCONCLUSIONSnAlthough MT has been associated with higher organ failure and complication rates, this risk appears to be reduced when blood products are delivered early in the resuscitation through a predefined protocol. Our institutions TEP was associated with a reduction in multiorgan failure and infectious complications, as well as an increase in ventilator-free days. In addition, implementation of this protocol was followed by a dramatic reduction in development of abdominal compartment syndrome and the incidence of open abdomens.

Early prediction of massive transfusion in trauma: Simple as ABC (Assessment of Blood Consumption)?

BACKGROUNDnMassive transfusion (MT) occurs in about 3% of civilian and 8% of military trauma patients. Although many centers have implemented MT protocols, most do not have a standardized initiation policy. The purpose of this study was to validate previously described MT scoring systems and compare these to a simplified nonlaboratory dependent scoring system (Assessment of Blood Consumption [ABC] score).nnnMETHODSnRetrospective cohort of all level I adult trauma patients transported directly from the scene (July 2005 to June 2006). Trauma-Associated Severe Hemorrhage (TASH) and McLaughlin scores calculated according to published methods. ABC score was assigned based on four nonweighted parameters: penetrating mechanism, positive focused assessment sonography for trauma, arrival systolic blood pressure of 90 mm Hg or less, and arrival heart rate > or = 120 bpm. Area under the receiver operating characteristic curve (AUROC) used to compare scoring systems.nnnRESULTSnFive hundred ninety-six patients were available for analysis; and the overall MT rate of 12.4%. Patients receiving MT had higher TASH (median, 6 vs. 13; p < 0.001), McLaughlin (median, 2.4 vs. 3.4; p < 0.001) and ABC (median, 1 vs. 2; p < 0.001) scores. TASH (AUROC = 0.842), McLaughlin (AUROC = 0.846), and ABC (AUROC = 0.842) scores were all good predictors of MT, and the difference between the scores was not statistically significant. ABC score of 2 or greater was 75% sensitive and 86% specific for predicting MT (correctly classified 85%).nnnCONCLUSIONSnThe ABC score, which uses nonlaboratory, nonweighted parameters, is a simple and accurate in identifying patients who will require MT as compared with those previously published scores.

Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients

ObjectiveAcute brain dysfunction or delirium occurs in the majority of mechanically ventilated (MV) medical intensive care unit (ICU) patients and is associated with increased mortality. Unfortunately delirium often goes undiagnosed as health care providers fail to recognize in particular the hypoactive form that is characterized by depressed consciousness without the positive symptoms such as agitation. Recently, clinical tools have been developed that help to diagnose delirium and determine the subtypes. Their use, however, has not been reported in surgical and trauma patients. The objective of this study was to identify the prevalence of the motoric subtypes of delirium in surgical and trauma ICU patients.MethodsAdult surgical and trauma ICU patients requiring MV longer than 24u202fh were prospectively evaluated for arousal and delirium using well validated instruments. Sedation and delirium were assessed using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method in the ICU (CAM-ICU), respectively. Patients were monitored for delirium for axa0maximum of 10u202fdays or until ICU discharge.PatientsA total of 100 ICU patients (46 surgical and 54 trauma) were enrolled in this study. Three patients were excluded from the final analysis because they stayed persistently comatose prior to their death.Measurements and resultsPrevalence of delirium was 70% for the entire study population with 73% surgical and 67% trauma ICU patients having delirium. Evaluation of the subtypes of delirium revealed that in surgical and trauma patients, hypoactive delirium (64% and 60%, respectively) was significantly more prevalent than the mixed (9% and 6%) and the pure hyperactive delirium (0% and 1%).ConclusionsThe prevalence of the hypoactive or “quiet” subtype of delirium in surgical and trauma ICU patients appears similar to that of previously published data in medical ICU patients. In the absence of active monitoring with axa0validated clinical instrument (CAM-ICU), however, this subtype of delirium goes undiagnosed and the prevalence of delirium in surgical and trauma ICU patients remains greatly underestimated.

Secondary abdominal compartment syndrome after severe extremity injury: are early, aggressive fluid resuscitation strategies to blame?

INTRODUCTIONnSecondary abdominal compartment syndrome (ACS) is the development of ACS in the absence of abdominal injury. The development of secondary ACS has been viewed by some authors as an unavoidable sequela of the aggressive crystalloid resuscitation often employed in the treatment of severe shock. We hypothesized that poor resuscitation techniques, including early and excessive crystalloid administration, places patients with extremity injuries at risk for developing secondary ACS.nnnMETHODSnThe Trauma Registry of the American College of Surgeons database was queried for all patients with an extremity Abbreviated Injury Scale (AIS) score of 3 or greater and abdominal AIS score of 0 treated at our institution between January 1, 2001 and December 31, 2005. The study group included those patients who developed secondary ACS, whereas the comparison cohort included those who did not develop secondary ACS.nnnRESULTSnForty-eight patients developed secondary ACS and were compared with 48 randomly selected patients who had an extremity AIS score of 3 or greater and an abdomen AIS score of 0. There were no differences between the groups with respect to age, sex, race, or individual AIS scores. However, the secondary ACS group had a slightly higher Injury Severity Score (25.6 vs. 21.4, p = 0.02), significantly higher operating room crystalloid administration (9.9 L vs. 2.7 L, p < 0.001), and more frequent use of a rapid infuser (12.5% vs. 0.0%, p = 0.01). Multiple logistic regression identified prehospital and emergency department crystalloid as predictors of secondary ACS.nnnCONCLUSIONSnAggressive resuscitation techniques, often begun in the prehospital setting, appear to increase the likelihood of patients with severe extremity injuries developing secondary ACS. Early, large volume crystalloid administration was the greatest predictor of secondary ACS.

Impact of high-dose antioxidants on outcomes in acutely injured patients

BACKGROUNDnThe profound oxidative stress that occurs following injury results in significant depletion of many endogenous antioxidants (vitamin C, E, selenium). Increasing evidence suggests antioxidant supplementation reduces infectious complications and organ dysfunction following injury and hemorrhagic shock. The purpose of this study was to evaluate the impact of high-dose antioxidant administration on the mortality rate of acutely injured patients.nnnMETHODSnIn October 2005, we implemented a 7-day high-dose antioxidant protocol for acutely injured patients admitted to our trauma center. A retrospective cohort study, evaluating all patients admitted to the trauma service between October 2005 and September 2006 following protocol implementation (AO+), was performed. The comparison cohort (AO-) was made up of those patients admitted in the year prior to protocol implementation.nnnRESULTSnA total of 4,294 patients met criteria (AO+, N = 2,272; AO-, N = 2022). Hospital (4 vs 3 days, P < .001) and ICU (3 vs 2 days, P = .001) median length of stays were significantly shorter in the AO+ group. Mortality was significantly lower in the AO+ group (6.1% vs 8.5%, P = .001), translating into a 28% relative risk reduction for mortality in patients exposed to high-dose antioxidants. After adjusting for age, gender, and probability of survival, AO exposure was associated with even lower mortality (OR 0.32, 95% CI 0.22-0.46). Patients with an expected survival <50% benefited most (OR 0.24, 95% CI 0.15-0.37).nnnCONCLUSIONSnA high-dose antioxidant protocol resulted in a 28% relative risk reduction in mortality and a significant reduction in both hospital and ICU length of stay. This protocol represents an inexpensive intervention to reduce mortality/morbidity in the trauma patient.

Use of Scene Vital Signs Improves TRISS Predicted Survival in Intubated Trauma Patients

INTRODUCTIONnThe Trauma Related Injury Severity Score (TRISS) has been previously validated to predict outcomes in nonintubated, nonparalyzed trauma patients. The purpose of this study was to assess the impact of scene vital signs on predicting survival in intubated trauma patients.nnnMETHODSnOur Trauma Registry of the American College of Surgeons was reviewed for all trauma patients admitted between 10/01/04 and 09/30/06, arriving by aeromedical transport. TRISS was evaluated for each patient based on their (1) scene vital signs and (2) arrival vital signs. Additionally, the TRISS-like score was calculated for each patient. Expected mortality for each score was measured against observed mortality.nnnRESULTSnFour thousand four hundred ninety-nine Trauma Registry of the American College of Surgeons patients were admitted during the study period; 695 (15%) were transported by air; 163 patients (23%) arrived intubated; 480 arrived nonintubated. Observed survival in the intubated group was 76%. Observed survival in the nonintubated group was 100%. TRISS using scene vital signs more closely predicted mortality among intubated patients than the other scoring systems (69% versus 39% using TRISS-arrival versus 80% using TRISS-like). Scene vital signs with TRISS also resulted in fewer unexpected outcomes (survivors and deaths).nnnCONCLUSIONSnTraditionally, patients arriving at trauma centers intubated are either excluded from the trauma registry or have their physiological score modified to account for pharmacologically altered respiratory rate and Glasgow Coma Scale. In intubated patients, TRISS using scene vital signs more reliably predicts survival and does so with far fewer unexpected outcomes than with other available scoring systems.